The mechanism by which certain cyclic AMP (cAMP) analogs exert lethal effects on tumor cells growing in culture and in animal hosts will be analyzed. Cells will be incubated with labelled analog and its metabolic fate will be determined by chromatography of acid-soluble extracts and nucleic acid digests. Cells resistant to the various analogs will be selected and analog metabolism and possible complementation by cell hybridization will be examined with these variants. Analog cross resistance will also be evaluated in resistant cells. Possible effects of analogs on the biosynthesis of purine and pyrimidine nucleotides, proteins, RNA and DNA will beexamined in wild-type and resistant cells. Efforts will be made to determine at which stage in the cell cycle different analogs exert their effects. Studies will be initiated to determine the efficacy of these analogs as therapeutic agents. Investigations of the potential cytotoxicity in animal hosts as well as the ability of the analogs to cause tumor regression as measured by tumor volume or increased lifespan will be conducted. These experiments will be done with the nucleoside counterparts of the cyclic nucleotide analogs to examine relative efficacies and also to examine the ability of the cyclic nucleotide analogs to affect those tumors produced using cells selected for resestance to the nucleoside analogs.